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Cell Biology of Lymphatic Metastasis The Potential Role of c-erbB Oncogene Signalling

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Lymphatic Metastasis and Sentinel Lymphonodectomy

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 157))

Abstract

Lymphatic metastases are an important indicator of the malignancy of epithelial cancers. Empirical clinical observations associating specific genetic abnormalities with tumour progression, allied with basic laboratory investigations, are providing not only improved prognostic and diagnostic opportunities, but also a detailed understanding of the molecular machinery of metastasis. One such association — between the c-erbB oncogene family and metastasis — has proved particularly instructive. Functional links between over-expression (and occasionally mutational activation) of c-erbB-1 (EGFR) and c-erbB-2 and specific phenotypes of metastatic cells have been elucidated. Activated c-erbB oncogenes potentiate tumour cell adhesion to endothelial cells and upregulate VEGF, potentially facilitating angiogenesis and vascular invasion. In addition, cells over-expressing these oncogenes frequently show aberrant cell-cell and cell-matrix interactions, mediated by changes in integrin and cadherin function. Thirdly, both EGFR and c-erbB-2 signalling can significantly upregulate specific matrix metalloproteinases, key enzymes involved in angiogenes is and invasion. Finally, c-erbB receptors linked to the actin cytoskeleton and highly expressed on invadopodia, are thought to assist cell migration. Taken together, these observations suggest that such receptors can act as “master switches” in metastasis, whose activation co-ordinately controls events normally utilised in development, now subverted by the metastatic cell. As such, they represent ideal targets for therapeutic intervention.

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  1. Tumour Biology and Metastasis, Section of Cancer Therapeutics, Institute of Cancer Research, Cotswold Rd, Sutton, Surrey, SM2 5NG, UK

    S. A. Eccles

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  1. S. A. Eccles
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  1. Klinik für Chirurgie und chirurgische Onkologie Robert-Rössle-Klinik, Universitätsklinikum Charité, Lindenberger Weg 80, 13122, Berlin, Germany

    Peter M. Schlag

  2. Istituto Europeo di Oncologia, Via Ripamonti 435, 20141, Milano, Italy

    Umberto Veronesi MD, PhD.

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Eccles, S.A. (2000). Cell Biology of Lymphatic Metastasis The Potential Role of c-erbB Oncogene Signalling. In: Schlag, P.M., Veronesi, U. (eds) Lymphatic Metastasis and Sentinel Lymphonodectomy. Recent Results in Cancer Research, vol 157. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-57151-0_5

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  • DOI: https://doi.org/10.1007/978-3-642-57151-0_5

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